Enhancing NK cell-mediated cytotoxicity to cisplatin-resistant lung cancer cells via MEK/Erk signaling inhibition

Abstract Major progress has been made clinically in inhibiting the programmed death receptor 1 (PD-1)/PD-L1 interaction to enhance T cell-mediated immune function, yet the effectiveness of anti-PD-L1/PD-1 agents in enhancing natural killer (NK) cell’s function remains largely unknown. Susceptibiliti...

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Autores principales:	Li Yang, MingJing Shen, Li Jun Xu, Xiaodong Yang, Ying Tsai, Peter C. Keng, Yuhchyau Chen, Soo Ok Lee
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c269617aaab84a4390a2877858fd746b
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spelling	oai:doaj.org-article:c269617aaab84a4390a2877858fd746b2021-12-02T15:06:24ZEnhancing NK cell-mediated cytotoxicity to cisplatin-resistant lung cancer cells via MEK/Erk signaling inhibition10.1038/s41598-017-08483-z2045-2322https://doaj.org/article/c269617aaab84a4390a2877858fd746b2017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-08483-zhttps://doaj.org/toc/2045-2322Abstract Major progress has been made clinically in inhibiting the programmed death receptor 1 (PD-1)/PD-L1 interaction to enhance T cell-mediated immune function, yet the effectiveness of anti-PD-L1/PD-1 agents in enhancing natural killer (NK) cell’s function remains largely unknown. Susceptibilities of cisplatin-resistant A549CisR and H157CisR cells vs. parental cells to the cytotoxic action of NK cells were examined. We found cisplatin-resistant cells more resistant to NK cell cytotoxicity than parental cells. There were constitutively higher expressions of PD-L1 in A549CisR and H157CisR cells than in parental cells in vitro, as well as in H157CisR cell-derived tumors than H157P cell-derived tumors. In contrast, we observed that the expression of PD-1 in NK cells was induced after co-culture with cisplatin-resistant cells. We also observed increased susceptibility of cisplatin-resistant cells to NK cell cytotoxicity when neutralizing antibody of PD-1 or PD-L1 was added. Further, we found that the NK group 2, member D (NKG2D) ligand levels were lower in A549CisR and H157CisR cells than in parental cells. Meanwhile, we discovered that the MEK/Erk signaling pathway played a significant role in this regulation, and the addition of a MEK/Erk pathway inhibitor significantly enhanced the PD-L1 Ab effect in enhancing NK cell cytotoxicity to cisplatin-resistant cells.Li YangMingJing ShenLi Jun XuXiaodong YangYing TsaiPeter C. KengYuhchyau ChenSoo Ok LeeNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Li Yang MingJing Shen Li Jun Xu Xiaodong Yang Ying Tsai Peter C. Keng Yuhchyau Chen Soo Ok Lee Enhancing NK cell-mediated cytotoxicity to cisplatin-resistant lung cancer cells via MEK/Erk signaling inhibition
description	Abstract Major progress has been made clinically in inhibiting the programmed death receptor 1 (PD-1)/PD-L1 interaction to enhance T cell-mediated immune function, yet the effectiveness of anti-PD-L1/PD-1 agents in enhancing natural killer (NK) cell’s function remains largely unknown. Susceptibilities of cisplatin-resistant A549CisR and H157CisR cells vs. parental cells to the cytotoxic action of NK cells were examined. We found cisplatin-resistant cells more resistant to NK cell cytotoxicity than parental cells. There were constitutively higher expressions of PD-L1 in A549CisR and H157CisR cells than in parental cells in vitro, as well as in H157CisR cell-derived tumors than H157P cell-derived tumors. In contrast, we observed that the expression of PD-1 in NK cells was induced after co-culture with cisplatin-resistant cells. We also observed increased susceptibility of cisplatin-resistant cells to NK cell cytotoxicity when neutralizing antibody of PD-1 or PD-L1 was added. Further, we found that the NK group 2, member D (NKG2D) ligand levels were lower in A549CisR and H157CisR cells than in parental cells. Meanwhile, we discovered that the MEK/Erk signaling pathway played a significant role in this regulation, and the addition of a MEK/Erk pathway inhibitor significantly enhanced the PD-L1 Ab effect in enhancing NK cell cytotoxicity to cisplatin-resistant cells.
format	article
author	Li Yang MingJing Shen Li Jun Xu Xiaodong Yang Ying Tsai Peter C. Keng Yuhchyau Chen Soo Ok Lee
author_facet	Li Yang MingJing Shen Li Jun Xu Xiaodong Yang Ying Tsai Peter C. Keng Yuhchyau Chen Soo Ok Lee
author_sort	Li Yang
title	Enhancing NK cell-mediated cytotoxicity to cisplatin-resistant lung cancer cells via MEK/Erk signaling inhibition
title_short	Enhancing NK cell-mediated cytotoxicity to cisplatin-resistant lung cancer cells via MEK/Erk signaling inhibition
title_full	Enhancing NK cell-mediated cytotoxicity to cisplatin-resistant lung cancer cells via MEK/Erk signaling inhibition
title_fullStr	Enhancing NK cell-mediated cytotoxicity to cisplatin-resistant lung cancer cells via MEK/Erk signaling inhibition
title_full_unstemmed	Enhancing NK cell-mediated cytotoxicity to cisplatin-resistant lung cancer cells via MEK/Erk signaling inhibition
title_sort	enhancing nk cell-mediated cytotoxicity to cisplatin-resistant lung cancer cells via mek/erk signaling inhibition
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/c269617aaab84a4390a2877858fd746b
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Enhancing NK cell-mediated cytotoxicity to cisplatin-resistant lung cancer cells via MEK/Erk signaling inhibition

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